The threat of radiological attacks has grown in recent years, warranting a concerted effort to translate the molecular advances of radiation research into bonafide medical products. These medical products must be directed toward the identification and treatment of attack victims who have received a radiation exposure in a critical dose range (approximately 2Gy to 8Gy). Left untreated, these victims die from complications of bone marrow failure. The purpose of the program is to (1) develop, test, and calibrate a biodosimeter to detect total body irradiation exposure in this critical range and (2) develop and test novel radioprotective agents to treat the bone marrow toxicity, and Gl toxicity, of radiation victims. To accomplish this goal, we have assembled four leading basic science investigators from related fields. Project 1 (Alan D'Andrea) will calibrate a biodosimeter and screen novel radioprotective drugs. Project 2 (David Livingston) will systematically develop and analyze biomarkers (immunofluorescence markers) of radiation damage and protection. Project 3 (Stephen Elledge) will use shRNA libraries to identify targets in radiation response pathways. Project 4 (Peter Sicinski) will employ novel genetic mouse models to study the role of cell cycle control in radiation sensitivity and resistance. The program is fortified by the establishment of three unique core facilities (the Mouse Biology and Stem Cell Core, the Institute of Chemistry and Chemical Biology Core, and the Radiation Clinical Trials Core). We have also created a novel Clinician-Scientist Training Program in order to develop the careers of young investigators in this area, and a Pilot Grant Program, to take advantage of the unique opportunities in Boston and to allow rapid redirection of resources, as needed. The program is designed to accelerate the development of new medical applications in the field of countermeasures against radiation.